PMID- 29956585 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20231103 IS - 1744-8069 (Electronic) IS - 1744-8069 (Linking) VI - 14 DP - 2018 Jan-Dec TI - Nuclear factor kappa B regulated monocyte chemoattractant protein-1/chemokine CC motif receptor-2 expressing in spinal cord contributes to the maintenance of cancer-induced bone pain in rats. PG - 1744806918788681 LID - 10.1177/1744806918788681 [doi] LID - 1744806918788681 AB - BACKGROUND: Chemokine, monocyte chemoattractant protein-1 (MCP-1), is a potential factor to cause cancer-induced bone pain (CIBP). NF-kappaB signaling is very important in mediating the expression of chemokines and may have a role in CIBP. However, the mechanism is still unclear. This study investigates the role of NF-kappaB in CIBP by regulating MCP-1/chemokine CC motif receptor-2 (CCR2) signaling pathway. METHODS: A rat CIBP model was established by injecting Walker-256 cells into the tibia medullary cavity. Nine days later, animals were intrathecally administrated with MCP-1 neutralizing antibody, CCR2 antagonist (RS504393), or NF-small ka, CyrillicB inhibitor (BAY11-7081). Mechanical paw withdrawal threshold was used to assess pain behavior and sciatic functional index, and radiographic images were adopted to evaluate the damage of nerve and bone. The spinal cords were harvested for Western blot and quantitative reverse transcription polymerase chain reaction. The distribution of MCP-1, CCR2, and NF-small ka, CyrillicB was detected by double immunofluorescent staining. RESULTS: CIBP caused remarkable bone destruction, injury of sciatic and femoral nerve, and persistent (>15 days) mechanical allodynia in rats. Tumor cell inoculation upregulate MCP-1 and NF-small ka, CyrillicB in activated neurons as well as CCR2 in neurons and microglia of the spinal cord. MCP-1 antibody, RS504393, and BAY11-7081 partially reversed CIBP-induced mechanical allodynia, and CIBP regulated the expression levels of pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma, and anti-inflammatory cytokine, interleukin 4, and BAY11-7081 lowered CIBP-induced MCP-1 and CCR2 expressions in a dose-dependent manner. CONCLUSION: In conclusion, NF-small ka, CyrillicB signaling pathway regulates the expressions of MCP-1/CCR2-induced inflammatory factors in the spinal cord of CIBP rats. FAU - Wang, Yungong AU - Wang Y AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Ni, Huadong AU - Ni H AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. AD - 2 The Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, China. FAU - Li, Hongbo AU - Li H AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Deng, Houshen AU - Deng H AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Xu, Long S AU - Xu LS AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Xu, Shijie AU - Xu S AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Zhen, Ying AU - Zhen Y AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Shen, Hui AU - Shen H AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Pan, Huan AU - Pan H AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. FAU - Yao, Ming AU - Yao M AUID- ORCID: 0000-0002-4226-8473 AD - 1 Department of Anesthesiology and Pain Medicine, First Affiliated Hospital of Jiaxing University, Jiaxing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180629 PL - United States TA - Mol Pain JT - Molecular pain JID - 101242662 RN - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile) RN - 0 (Antibodies) RN - 0 (Benzoxazines) RN - 0 (Ccr2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Nitriles) RN - 0 (RS 504393) RN - 0 (Receptors, CCR2) RN - 0 (Spiro Compounds) RN - 0 (Sulfones) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) SB - IM MH - Animals MH - Antibodies/therapeutic use MH - Benzoxazines/therapeutic use MH - Bone Neoplasms/complications/diagnostic imaging MH - Cancer Pain/diagnostic imaging/etiology/*pathology MH - Cell Line, Tumor MH - Chemokine CCL2/immunology/*metabolism MH - Cytokines/metabolism MH - Disease Models, Animal MH - Female MH - NF-kappa B/*metabolism MH - Nitriles/therapeutic use MH - Pain Threshold/drug effects MH - Phosphopyruvate Hydratase/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, CCR2/*metabolism MH - Spinal Cord/*metabolism MH - Spiro Compounds/therapeutic use MH - Sulfones/therapeutic use MH - Time Factors MH - Up-Regulation/drug effects PMC - PMC6055241 OTO - NOTNLM OT - Cancer-induced bone pain OT - MCP-1/CCR2 axis OT - NF-kappaB signaling pathway OT - astrocytes OT - chemokines OT - neurons EDAT- 2018/06/30 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/06/29 CRDT- 2018/06/30 06:00 PHST- 2018/06/30 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/06/30 06:00 [entrez] PHST- 2018/06/29 00:00 [pmc-release] AID - 10.1177_1744806918788681 [pii] AID - 10.1177/1744806918788681 [doi] PST - ppublish SO - Mol Pain. 2018 Jan-Dec;14:1744806918788681. doi: 10.1177/1744806918788681. Epub 2018 Jun 29.